Wnt Signaling and Its Impact on Mitochondrial and Cell Cycle Dynamics in Pluripotent Stem Cells

Abstract

The core transcriptional network regulating stem cell self-renewal and pluripotency remains an intense area of research. Increasing evidence indicates that modified regulation of basic cellular processes such as mitochondrial dynamics, apoptosis, and cell cycle are also essential for pluripotent stem cell identity and fate decisions. Here, we review evidence for Wnt regulation of pluripotency and self-renewal, and its connections to emerging features of pluripotent stem cells, including (1) increased mitochondrial fragmentation, (2) increased sensitivity to cell death, and (3) shortened cell cycle. We provide a general overview of the stem cell–specific mechanisms involved in the maintenance of these uncharacterized hallmarks of pluripotency and highlight potential links to the Wnt signaling pathway. Given the physiological importance of stem cells and their enormous potential for regenerative medicine, understanding fundamental mechanisms mediating the crosstalk between Wnt, organelle-dynamics, apoptosis, and cell cycle will be crucial to gain insight into the regulation of stemness.

Retinol/inflammation affect stemness and differentiation potential of gingival stem/progenitor cells via Wnt/β‐catenin

“…It has been suggested that Vitamin A and Wnt/β-catenin signaling have complementary roles in anterior-posterior patterning, 32 while Wnt/β-catenin signaling is crucial for stem/progenitor cells osteogenic differentiation by interacting with several nuclear receptors, including the retinoic acid receptor. 22 In the current study, retinol and inflammatory stimulation of G-MSCs activated the canonical Wnt/β-catenin pathway, resulting in a significant degradation and reduction in intracellular β-catenin levels, feasibly affecting their cellular stemness, 33 proliferative, 34 and differentiation aptitude. 35 The present experiment examined the effect of the inflammatory "cocktail" together with retinol on the expression of the major pluripotency markers Nanog, Oct4, and Sox2 at 24, 72, and 120 hours.…”

Parkinson's disease, aging and adult neurogenesis: Wnt/β‐catenin signalling as the key to unlock the mystery of endogenous brain repair

“…Owing to the potential associations between the Wnt pathway and mitochondrial dynamics, apoptosis, and the cell cycle, which in turn affect NSC self‐renewal and differentiation (Beckervordersandforth, ; Beckervordersandforth et al, ; Chandle et al, ; Chong, Shang, Hou, & Maiese, ; Rasmussen et al, ; Richetin et al, ; Singh, Mishra, Bharti, et al, ; Walter et al, ), we herein highlight the role of WβC ‐ signalling and its crosstalk with astrocyte‐ and microglial‐derived oxidative and inflammatory pathways in the regulation of adult neurogenesis in PD. Particular attention is paid to the exacerbated inflammation and oxidative stress associated with the upregulation of endogenous Wnt‐inhibitors.…”

Impaired Mitochondrial ATP Production Downregulates Wnt Signaling via ER Stress Induction

“…Alternatively, activation of Wnt-induced pathways was proposed as a strategy to promote axonal growth after injury (Garcia et al, 2018). While Wnt signaling is well known to influence mitochondrial function (e.g., Rasmussen et al, 2018;Yoon et al, 2010), the possibility that pharmacological agents affecting mitochondrial metabolism specifically and systematically modulate Wnt signaling has not been explored so far. Here, we show that the fine-tuning of mitochondrial function leads to Wnt signaling modulation both in vitro and in vivo, and we identify the underlying mechanism.…”